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Blood, 15 March 2005, Vol. 105, No. 6, pp. 2300-2306.
Prepublished online as a Blood First Edition Paper on November 30, 2004; DOI 10.1182/blood-2004-04-1473.
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Submitted April 16, 2004
Accepted November 15, 2004
Engraftment and survival following reduced-intensity allogeneic peripheral blood hematopoietic cell transplantation is affected by CD8+ T-cell dose
Thai M Cao*, Judith A Shizuru, Ruby M Wong, Kevin Sheehan, Ginna G Laport, Keith E Stockerl-Goldstein, Laura J Johnston, Monic J Stuart, Janice M Brown, F C Grumet, Robert S Negrin, and Robert Lowsky
Division of Blood and Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA; Division of Hematology, Department of Medicine, Current Address: University of Utah School of Medicine, Salt Lake City, UT, USA
Division of Blood and Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
Department of Health Research and Policy, Stanford University, Stanford, CA, USA
Stanford Cellular Therapeutics and Transplantation Laboratory, Stanford Hospital and Clinics, Stanford, CA, USA
Histocompatibility Laboratory, Stanford Medical School Blood Center, Palo Alto, CA, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
* Corresponding author; email: thai.cao{at}hsc.utah.edu.
The influence of graft composition on clinical outcomes after reduced-intensity conditioning is not well characterized. In this report we prospectively enumerated CD34+, CD3+, CD4+, and CD8+ cell doses in granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell (G-PBMC) allografts in 63 patients transplanted following non-myeloablative conditioning with total body irradiation 200 cGy plus fludarabine as treatment for malignant diseases. Donors were HLA-identical siblings (n = 38) or HLA-matched unrelated individuals (n = 25). By univariate analyses G-PBMC CD8+ T-cell dose the 50th percentile favorably correlated with full donor blood T-cell chimerism (P = .03), freedom from progression (P = .001) and overall survival (P = .03). No G-PBMC cell dose influenced grade II - IV acute or extensive chronic graft-versus-host disease. In multivariate analysis only G-PBMC CD8+ T-cell dose (P = .003; RR = 0.2, 95% CI = 0.1-0.6) was associated with improved freedom from progression. Infusion of low G-PBMC CD8+ T-cell dose for non-myeloablative allografting may adversely affect T-cell engraftment and survival outcome.

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